Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial

Patel, Manish R.; Ellerton, John; Infante, Jeffrey R.; Agrawal, Manish; Gordon, Michael; Aljumaily, Raid; Britten, Carolyn D.; Dirix, Luc; Lee, Moon Hyoung; Taylor, M.H.; Schöffski, Patrick; Wang, Ding; Ravaud, Alain; Gelb, Arnold B.; Xiong, Junyuan; Rosen, Galit; Gulley, James L.; Apolo, Andrea B.

doi:10.1016/s1470-2045(17)30900-2

Cited by 521 publications

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References 31 publications

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“…Confirmed ORR was 17%, including 6% CR, 11% partial response (PR), and median OS 6.5 months. This ORR was observed (24%) in the high PD-L1 expression group (defined in this study as ≥5% staining of tumor cells only) [28]. Safety profiles showed a low rate of grade 3 to 4 TRAEs (8%) and no treatment-related deaths.…”

Section: Immune Checkpoint Inhibitors After Platinum-based Chemotheramentioning

confidence: 65%

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Immune checkpoint inhibitors for urothelial carcinoma

Kim

Seo

2018

Investig Clin Urol

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Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is the most common histological type of cancer. Currently, platinum-based cytotoxic chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant therapeutic option in non-muscle invasive bladder cancer (NMIBC) after transurethral resection, to prevent recurrence and progression. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of UC. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. To date, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US-FDA) for first- or second-line use in mUC, based on durable therapeutic response and manageable safety profiles observed in relevant clinical trials. In addition, the clinical use of several immune checkpoint inhibitors is currently being tested for MIBC and NMIBC. In this article, we review the current and ongoing clinical trials, regarding immune checkpoint inhibitors, being conducted in various clinical settings of UC, including mUC, MIBC, and NMIBC.

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Section: Immune Checkpoint Inhibitors After Platinum-based Chemotheramentioning

confidence: 65%

“…In a phase Ib trial, avelumab showed clinical efficacy in patients with platinum-refractory mUC (JAVELIN Solid Tumor trial, NCT01772004) [28]. Confirmed ORR was 17%, including 6% CR, 11% partial response (PR), and median OS 6.5 months.…”

Section: Immune Checkpoint Inhibitors After Platinum-based Chemotheramentioning

confidence: 99%

Immune checkpoint inhibitors for urothelial carcinoma

Kim

Seo

2018

Investig Clin Urol

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“…Avelumab, an anti‐PD‐L1 antibody, received accelerated FDA approval for UC patients in the second‐line setting after platinum‐based chemotherapy. The approval was based on the data from the open‐label, single‐arm, phase I dose‐expansion JAVERIN Solid Tumor study . The study analyzed 249 UC patients who had experienced progression after at least one previous platinum‐based chemotherapy or who were cisplatin‐ineligible patients.…”

Section: Immunotherapy In Ucmentioning

confidence: 99%

Immunotherapy for genitourinary tumors

Nakayama

Kitano

2019

Int J of Urology

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The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.

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“…Severe AEs (grade 3–4) and grade 3–4 immune-mediated AEs occurred in 6.8 and 2.1% of the patients, respectively[11]AvelumabBavencioPD-L110 mg/kg, every 2 weeks1JAVELIN161The ORR was 17% including 6% with CR. Severe (grade 3–4) treatment-related AEs occurred in 8%[12] PD-1 programmed death 1 , PD-L1 programmed death ligand 1, OS overall survival, ORR objective response rate, CR complete response, AE adverse event, Reference the reference number in this review article …”

Section: Introductionmentioning

confidence: 99%

“…The most frequent AEs (of any grade in ≥ 10% patients) were infusion-related reaction (29%, all grade 1–2) and fatigue (16%). Severe (grade 3–4) treatment-related AEs occurred in 8%; the most common of these were fatigue (2%) and asthenia, elevated lipase, hypophosphatemia, and pneumonitis (1%) [12]. It is worth remembering that avelumab causes infusion-related reactions frequently, whereas this is seldom seen in the other checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in medical therapy for metastatic urothelial cancer

2018

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Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.

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Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial

Abstract: Merck KGaA, and Pfizer Inc.

Cited by 521 publications

References 31 publications

Immune checkpoint inhibitors for urothelial carcinoma

Immune checkpoint inhibitors for urothelial carcinoma

Immunotherapy for genitourinary tumors

Recent advances in medical therapy for metastatic urothelial cancer

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